Studies are conducted to better define the mechanisms involved in tumor growth and spread (i.e. metastases). Most human tumors cannot be studied in vitro because they grow poorly in culture and in nude mice (less than 5% grow). Previously we found that tumor cells grow well in vitro when exposed to a basement membrane substratum. When tumor cells are premixed with a basement membrane mixture (matrigel) and injected subcutaneously, rapid growth of all tumors studied to date is observed. Tumor metastasis requires that the cells adhere to the vessel basement membrane, degrade it and migrate through. Laminin is a potent inducer of collagenase, and we find that a synthetic peptide from laminin of 18 amino acids promotes collagenase IV activity and tumor metastases. This peptide also induces collagenase IV activity in non malignant cells and makes them have an invasive phenotype. Likewise, transfection of tumor cells with this enzyme results in increased tumor spread. In related studies, we find that TGF-beta reduces the invasive phenotype by increasing the synthesis of a collagenase inhibitor, TIMP (tissue inhibitor of metalloproteinase). Our goal is to better understand the malignant phenotype to devise diagnostic and therapeutic strategies to reduce tumor growth and spread.